ROS production is proportional to the increase in mitochondrial respiration and
electron chain activity. Numerous factors (including radiations, oxygen shortage,
carcinogens and inflammation) can give rise to ROS, ultimately leading to ROS-
mediated genomic instability and cancer. Under normal conditions, the balance
between ROS levels are tightly controlled by an inducible antioxidant program
that responds to cellular stressor, including enzymes such as superoxide
dismutase, catalase, and those involved in glutathione metabolism. Some
components of the ROS scavenging pathway are linked to mitochondrial
oxidative metabolism by the PGC-l coactivators that enable cells to maintain
normal redox status in response to changing oxidative capacity. The increase in
mitochondrial number stimulated by these proteins could cause an increase in the
production of ROS. Therefore, if ROS production were proportional to the
increase of electron transport activity stimulated by the PGC-l proteins, these
molecules would ultimately drive ROS levels higher. However, PGC-la is able
to upgrade aerobic energy metabolism in tissues with high aerobic demand
promoting ROS formation on one hand and ROS scavenging .systems on the
other.
Since the role of PGC-l ß in this process is completely unknown and ROS
production is .commonly linked to mitochondrial dysfunctions that, in turn, are
linked with several diseases, such as intestinal cancer and several metabolic
diseases including steatohepatitis, we decided to investigate whether PGC-l ß
could be involved in the mitochondrial homeostasis and ROS generation in two
different organs, the intestine and the liver.